Interrogation of changes in the contents of a sealed container

• US 7,407,796 B2
• Filed: 05/06/2004
• Issued: 08/05/2008
• Est. Priority Date: 01/31/2000
• Status: Expired due to Fees

• Current Assignee: Penn State Research Foundation
• Original Assignee: Penn State Research Foundation
• Inventors: Hammerstedt, Roy H., Phillips, Allen T.
• Primary Examiner(s): Chin; Christopher L
• Application Number:
  US10/840,178
• Publication Number:
  US 20040206658A1
• Time in Patent Office: 1,552 Days
• Field of Search: 435/287.4, 435/287.6, 435/287.7, 435/287.8, 435/287.9, 435/288.7
• US Class Current: 435/287.2
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 2021/7796 Special mountings, packaging of indicators
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/80 Indicating pH value
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

A device and method allowing evaluation of the contents of a sealed primary container by means of an integral sensor which is separated from the contents of the sealed primary container yet provides information on quality of the contents of the primary container without breaking the sealed system. The integral sensor device includes a biosensor retained within a plastic construct by a gated-pore membrane. Pores in the membrane open in response to an environmental change in the primary container allowing the contents of the primary container to contact the biosensor. Status of the contents of the primary container can be determined by inspection of the biosensor, visually or via a fiberoptic probe, through the optical window of the plastic construct.

Claims

1. A sensor device, comprising:

a biosensor comprising a receptor bound on a solid substrate;

a sensor compartment having an interior and an exterior, and enclosing the biosensor, the sensor compartment having a surface allowing external viewing of the biosensor; and

a separation barrier forming at least a portion of the sensor compartment, the separation barrier being selected from the group consisting of a fibril membrane, a microporous membrane and a capillary-pore membrane, the separation barrier having at least one pore allowing fluid communication between the interior and the exterior of the sensor compartment, wherein the biosensor further comprises a detector molecule and signal material which are each attached to a surface of the biosensor wherein the detector molecule and signal material are selected from the group consisting of a) a combination of a first fluorescent receptor and a second fluorescent receptor, the second fluorescent receptor emitting detectable light of a unique wavelength on excitation by fluorescent resonance transfer by the first fluorescent receptor;

b) a combination of a first receptor and a second receptor, the first receptor binding a cell and the second receptor undergoing a detectable spectral change in response to material released by the cell bound to the first receptor;

c) a combination of two inhibited fluorescent groups linked by an enzymatic cleavage site, and wherein enzymatic action cleaves the enzymatic cleavage site and releases the fluorescent inhibition; and

d) a combination of a first receptor and a second receptor, the first receptor binding a cell capable of releasing an enzyme and the second receptor being an inhibited fluorescent group wherein the enzyme releases the fluorescent inhibition.

2. The sensor device of claim 1, wherein the separation barrier separates the interior of the sensor compartment from a primary container.

3. The sensor device of claim 2, wherein the primary container is closed for analysis.

4. The sensor device of claim 1, wherein the at least one pore which allows fluid communication between the interior and exterior of the sensor compartment is occluded with a responsive material.

5. The sensor device of claim 4, wherein the responsive material is selected from the group consisting of cellulosics, non-cellulosic non-protein polymers, protein polymers, lipid bilayers, and lipid-containing composites.

6. The sensor device of claim 4, wherein the responsive material exhibits a response selected from the group consisting of eroding, dissolving, and changing three-dimensional form.

7. The sensor device of claim 6, wherein the response results from a change selected from the group consisting of a change in solvent concentration, a change in pH, a change in temperature, bacterial action, endotoxin action, enzymatic action, and contact with water.

8. The sensor device of claim 1, wherein the sensor compartment has walls comprised of an opaque material.

9. The sensor device of claim 1, wherein the bioactive detector molecule and signal material are a fluorescent receptor complex.

10. The sensor device of claim 1, wherein the bioactive detector molecule and signal material are a fluorochrome-receptor complex.

11. The sensor device of claim 1, wherein the device is capable of aseptic operation.

12. The sensor device of claim 1, wherein the external viewing is remote viewing.

13. A sensor device, comprising:

a biosensor comprising a receptor bound on a solid substrate;

a sensor compartment having an interior and an exterior, and enclosing the biosensor, the sensor compartment having a surface allowing external viewing of the biosensor; and

a separation barrier fonning at least a portion of the sensor compartment, the separation barrier being selected from the group consisting of a fibril membrane, a microporous membrane and a capillary-pore membrane, the separation barrier having at least one pore allowing fluid conununication between the interior and the exterior of the sensor compartment, wherein the biosensor further comprises a bioactive detector molecule and signal material which are each attached to a surface of the biosensor wherein the bioactive detector molecule and signal material are selected from the group consisting of a) a combination of a first fluorescent receptor and a second fluorescent receptor, the second fluorescent receptor emitting detectable light of a unique wavelength on excitation by fluorescent resonance transfer by the first fluorescent receptor;

b) a combination of a first receptor and a second receptor, the first receptor binding a cell and the second receptor undergoing a detectable spectral change in response to material released by the cell bound to the first receptor;

c) a combination of two inhibited fluorescent groups linked by an enzymatic cleavage site, and wherein enzymatic action cleaves the enzymatic cleavage site and releases the fluorescent inhibition;

d) a combination of a first receptor and a second receptor, the first receptor binding a cell capable of releasing an enzyme and the second receptor being an inhibited fluorescent group wherein the enzyme releases the fluorescent inhibition; and

e) a receptor that binds a material, such that upon binding the material, spectral features of the receptor are altered.